This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Plasmodium falciparum is a purine auxotroph, salvaging purines from erythrocytes for synthesis of RNA and DNA. Hypoxanthine is the key precursor for purine metabolism in Plasmodium. Adenosine deaminase is one of key enzymes to salvage hypoxanthine from adenosine in this parasite and the coformycin-derivates represent a promising class of potent natural-product transition state analogue inhibitors of malarial adenosine deaminase. Recognition of a methylthio-adenosine substrate by malarial, but not human, adenosine deaminase underlies selective inhibition by methylthio-coformycin.